Adenosine-induced bronchoconstriction in asthma: Role of mast cell-mediator release

Cushley, M. J.; Holgate, S. T.

doi:10.1016/0091-6749(85)90057-0

Cited by 125 publications

(71 citation statements)

References 30 publications

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“…Adenosine or its precursor, AMP, can elicit bronchoconstriction in asthmatic (7) and COPD patients (8) while having little effect on normal individuals. In asthmatics, this response appears to be mediated by adenosine-induced mast cell degranulation in the airways (9,10). These data point to a proinflammatory role for adenosine during the acute phases of asthma.…”

Section: Introductionmentioning

confidence: 70%

A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury

Sun¹,

Young²,

Molina³

et al. 2005

J. Clin. Invest.

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Adenosine is a signaling nucleoside that has been implicated in the regulation of asthma and chronic obstructive pulmonary disease. Adenosine signaling can serve both pro-and anti-inflammatory functions in tissues and cells. In this study we examined the contribution of A 1 adenosine receptor (A 1 AR) signaling to the pulmonary inflammation and injury seen in adenosine deaminase-deficient (ADA-deficient) mice, which exhibit elevated adenosine levels. Experiments revealed that transcript levels for the A 1 AR were elevated in the lungs of ADA-deficient mice, in which expression was localized predominantly to alveolar macrophages. Genetic removal of the A 1 AR from ADA-deficient mice resulted in enhanced pulmonary inflammation along with increased mucus metaplasia and alveolar destruction. These changes were associated with the exaggerated expression of the Th2 cytokines IL-4 and IL-13 in the lungs, together with increased expression of chemokines and matrix metalloproteinases. These findings demonstrate that the A 1 AR plays an anti-inflammatory and/or protective role in the pulmonary phenotype seen in ADA-deficient mice, which suggests that A 1 AR signaling may serve to regulate the severity of pulmonary inflammation and remodeling seen in chronic lung diseases by controlling the levels of important mediators of pulmonary inflammation and damage.

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Section: Introductionmentioning

confidence: 70%

A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury

Sun¹,

Young²,

Molina³

et al. 2005

J. Clin. Invest.

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“…Although adenosine has little effect on normal human airway smooth muscle in vitro, it causes constriction of asthmatic airways in vitro and bronchoconstriction in asthmatic subjects when given by inhalation [31,32]. The mechanism of bronchoconstriction is indirect, and involves release of histamine and leukotrienes from airway mast cells [32,33]. The bronchoconstrictor effect of adenosine is prevented by therapeutic concentrations of theophylline [34].…”

Section: Adenosine Receptor Antagonismmentioning

confidence: 99%

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

250

107

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T Th he eo op ph hy yl ll li in ne e i in n t th he e m ma an na ag ge em me en nt t o of f a as st th hm ma a: : t ti im me e f fo or r r re ea ap pp pr ra ai is sa al l? ?P.J. Barnes*, R.A. Pauwels** Theophylline is now considered to be a bronchodilator, but it is increasingly recognized that theophylline has other anti-asthma activities, which may be more important. Theophylline, even at low plasma concentrations, inhibits the late asthmatic reaction following allergen challenge. These clinical pharmacological observations are substantiated by experimental animal and in vitro data showing that theophylline has several anti-inflammatory activities relevant to asthma. These include the inhibition of cytokine synthesis and release, the inhibition of inflammatory cell activation and microvascular leakage, and the prevention of airway hyperresponsiveness induced by airway inflammation. Theophylline appears to have immunomodulatory effects, even at relatively low plasma concentrations.Based on these considerations, theophylline can be regarded as a useful alternative to other anti-inflammatory drugs for the chronic treatment of mild to moderate asthma. Theophylline should be used at lower doses to achieve plasma concentrations of 5-10 mg·l -1 , which will avoid the risk of side-effects.Further studies are required to evaluate the role of low-dose theophylline as an adjunct to low-dose inhaled steroids in the management of chronic asthma. It may now be appropriate to re-evaluate the role of theophylline in asthma management.

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“…Methacholine-and histamine-induced bronchoconstriction are likely to be due to a direct effect of these agonists on speci®c receptors on the airway smooth muscle. In contrast, the bronchoconstriction caused by inhalation of adenosine 59-monophosphate (AMP), appears to be largely due to histamine release from primed airway mast cells [2]. Although airway responsiveness is usually measured with histamine and methacholine challenges [3], bronchial response to inhaled AMP has also been used to assess airway responsiveness [4±6].…”

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confidence: 99%

Bronchoconstriction induced by inhaled adenosine 5′-monophosphate in subjects with allergic rhinitis

et al. 2001

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Bronchoconstriction induced by inhaled adenosine 59-monophosphate in subjects with allergic rhinitis. L. Prieto, V. Gutie Ârrez, J. Lin Äana, J. Marõ Ân. #ERS Journals Ltd 2001. ABSTRACT: Adenosine and its related nucleotide, adenosine 59-monophosphate (AMP) induce bronchoconstriction in asthmatics, probably caused by histamine release from airway mast cells. The objective of this study was to determine the effect of inhaled AMP on lung function in subjects with allergic rhinitis.A total of 52 adults (28 subjects with allergic rhinitis, 14 asthmatics and 10 healthy subjects) were challenged with increasing concentrations of AMP and methacholine. Air¯ow was assessed after each concentration and the response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall (PC20) in forced expired volume in one second (FEV1).All 14 asthmatics, 10 subjects with allergic rhinitis and none of the healthy controls were hyperresponsive to AMP. Subjects with allergic rhinitis had higher prevalence of hyperresponsiveness to AMP than healthy controls (p=0.038). Although the prevalence of hyperresponsiveness for methacholine and for AMP in subjects with allergic rhinitis was similar (39% and 36%, respectively), four subjects had hyperresponsiveness to methacholine but not to AMP, whereas three subjects had hyperresponsiveness to AMP but not to methacholine.To conclude, inhaled adenosine 59-monophosphate causes airway narrowing in a signi®cantly higher proportion of subjects with allergic rhinitis than healthy volunteers. Furthermore, methacholine and adenosine 59-monophosphate hyperresponsiveness are not detected in the same individuals with allergic rhinitis, thus suggesting that responsiveness to the two bronchoconstrictor stimuli is not re¯ecting the same abnormalities of the airways. Eur Respir J 2001; 17: 64±70. Seccio Â n de Alergologõ Âa and Universidad de Valencia, Valencia, Spain (The NAOMI project).

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Adenosine-induced bronchoconstriction in asthma: Role of mast cell-mediator release

Cited by 125 publications

References 30 publications

A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury

A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury

Theophylline in the management of asthma: time for reappraisal?

Bronchoconstriction induced by inhaled adenosine 5′-monophosphate in subjects with allergic rhinitis

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